NUTRITIONAL REGULATION OF CELL AND ORGAN GROWTH, DIFFERENTIATION, AND DEVELOPMENT
Location: Children Nutrition Research Center (Houston, Tx)
Title: Positive net movements of amino acids in the hindlimb after overnight food deprivation contribute to sustaining the elevated anabolism of neonatal pigs
Submitted to: Journal of Applied Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 14, 2008
Publication Date: September 18, 2008
Citation: Thivierge, M.C., Bush, J.A., Suryawan, A., Nguyen, H.V., Orellana, R.A., Burrin, D.G., Jahoor, F., Davis, T.A. 2008. Positive net movements of amino acids in the hindlimb after overnight food deprivation contribute to sustaining the elevated anabolism of neonatal pigs. Journal of Applied Physiology. 105(6):1959-1966.
Interpretive Summary: Growth is very rapid in the newborn, due to the high rate of synthesis of proteins and reduced rate of breakdown of proteins in the whole body after eating. Skeletal muscle grows at a faster rate than other tissues in the newborn, and we have previously shown that this is in part due to the increase in the synthesis of muscle proteins after feeding. However, less is known about the regulation of protein breakdown in the muscle of newborns. Using the baby pig as an animal model, we investigated the movement of amino acids, which are the building blocks of protein, into and out of the muscle and protein degradation in muscle in different ages of pigs during the feeding and fasting cycles. We found that during short periods of fasting, protein degradation in skeletal muscle of newborns is not increased. Amino acids are taken up by muscle during short fasting periods to maintain cellular concentrations of amino acids to sustain neonatal protein synthesis. Thus, the finely tuned regulation of protein accretion in newborns involves tightly regulated protein synthesis, protein breakdown, and cellular exchanges of amino acids. This results in the rapid growth of muscle growth in the newborn. These findings are important because by identifying the mechanism that regulates muscle growth in neonates we can learn valuable information to develop better strategies for the nutritional management of low birth weight infants.
During the neonatal period, high protein breakdown rate is a metabolic process inherent to elevated rates of protein accretion in skeletal muscle. To determine the relationship between hindlimb net movements of essential and nonessential amino acids in the regulation of hindlimb protein breakdown during an overnight fasting-feeding cycle, we infused overnight-food-deprived 10- and 28-day-old piglets with [1-(13)C]phenylalanine and ["ring"-(2)H]tyrosine over 7 h (during 3 h of fasting and then during 4 h of feeding). Extraction rates for aspartate and glutamate after an overnight fast were 15% and 51% in the 10-day-old compared with 6% and 25% in the 28-day-old ("P" < 0.05) piglets, suggesting an altered requirement for precursors of amino acids to shuttle nitrogen to the liver as early life progresses. This occurred simultaneously with marginal positive hindlimb net balance of essential amino acids after an overnight fast, with negative net release of many nonessential amino acids, such as alanine, asparagine, glutamine, glycine, and proline. This suggests that newborn muscle does not undergo significant protein mobilization after a short period of fasting in support of an elevated rate of protein accretion. Furthermore, tyrosine efflux from hindlimb breakdown between overnight fasting and feeding periods was not different in the 10-day-old piglets, for which tyrosine was limiting, but when tyrosine supply balanced requirements in the 28-day-old piglet, hindlimb efflux was increased ("P" = 0.01). The results of the present study indicate that proteolysis and net movements of amino acids are coordinated mechanisms that sustain the elevated rate of net protein accretion during overnight feeding-fasting cycles in the neonate.